title: Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles.
abstract: Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Huang
authors.forename: Lizhen
authors.initials: L
authors.lastname: He
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.forename: Cundong
authors.initials: C
authors.lastname: Fan
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Yum-Shing
authors.initials: YS
authors.lastname: Wong
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012643:Selenium / Q000737:chemistry*; D014168:Transferrin / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D014168:Transferrin; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D012643:Selenium